Previous studies during the preceding grant period demonstrated that murine bone marrow contains a population of "null" lymphocytes which respond to PHA blastogenesis, proliferation and expression of surface T cell phenotype. In contrast to peripheral PHA responsive cells, these small lymphocytes do not recirculate, are rapidly renewed and are present in nude mouse bone marrow but not in LN and SPL. The known characteristics of these "pre-T cells" do not match any type of T cell precursor described by other assays and these cells may represent an alternative pathway of T cell development. The capacity of these cells for maturing under thymic influence or, independent of it, into cells capable of reacting in MLR, GVH and DTH to H2 antigens will be studied after they have been exposed to thymic epithelial monolayers, cAMP or to alloantigens in intact or thymectomized F1 hosts. It is known that bone marrow cells synergize with immune T cells in controlling the growth rate of tumors, and the role of bone marrow "pre-T cells" phenomenon will be investigated using 3-methylcholanthrene induced sarcomas in mice. Following topical labeling of the bone marrow with 3H-TdR, the in vivo development of surface Thy-1 or brain associated antigen will be looked for on 3H-labeled cells that had migrated to the SPL, LN and THY, duplicating our studies on bone marrow derived B cells. The relationship of pre-T cells to prothymocytes and postthymic T cell precursors will be investigated making use of experimental models such as thymic atrophy consequent upon 89Sr treatment and serial transfer of chromosomally marked, selected bone marrow populations. The relationship of pre B cells and pre-T cells will be explored in mu-suppressed and nude mice, as well as in regenerating bone marrow devoid of prothymocytes. Competition for expression of T or B cell surface phenotypes by bone marrow pre-B cells will be studied using specific and nonspecific inducing agents in vitro. The in vivo and in vitro studies will comprehensively characterize "pre-T cells" produced in the BM at a sustained and rapid rate, and will define their status with respect to T cell production.